**3. Vitamin B12 and diabetes**

The connection between diabetes and vitamin B12 can be explained as:

#### **3.1 Vitamin B12 deficiency and type 1 diabetes mellitus**

Diabetes Type 1 is an automatic immune state which is the outcome from auto immune devastation for insulin releasing from beta cells of pancreas. This can be consistently related to new organ as well as non-organ particular auto immune plus endocrine situations results in growth of autoimmune polyglandular disorders [33].

Pernicious anemia due to chronic autoimmune gastritis can be very much widespread amongst people having type 1 diabetes. Pernicious anemia and Chronic autoimmune gastritis are present within almost 2% as well as up to 1% common people correspondingly. Amongst people having type 1 diabetes, incidence raises 3 to 5 times [34]. vitamin B12 shortage because of pernicious anemia present repeatedly amongst individuals having type 1 diabetes.

Individuals suffering from type 1 diabetes show parietal cell antibodies (PCA) plus auto antibodies to intrinsic factor (AIF) type 1 as well as 2 (De Block *et al*., 1999) in particular people having antibodies of glutamate decarboxylase-65 (GAD-65) as well as HLA-DQA1\*0501-B1\*0301 haplotype [35]. The PCA hampers release for intrinsic factor leading to pernicious anemia, state that can be 10 times further prevailing amongst people having type 1 DM as well as people do not have DM. Type 1 AIF lead to vitamin B12 deficit inhibiting attachment of vitamin B12 to IF. This inhibits transport toward assimilation spot, terminal ileum. Such auto antibodies can be present within 70% people suffering from pernicious anemia.

Main autoimmune hypothyroidism as well as celiac ailment is common comorbidities between people having type 1 diabetes [36] and directly influence vitamin B12 metabolism. Vitamin B12 shortage between people having autoimmune hypothyroidism is described as existence of gastric parietal cell antibodies as well as intrinsic factor, decreased ingestion by mouth because of thyroid hormone insufficiency as well as flawed assimilation because of bowel wall edema, decreased bowel motility and increased growth of bacteria [37]. Celiac disease can be greatly widespread autoimmune mediated gastrointestinal state happen within 1–16% people having type 1 diabetes in contrast to 0.3–1% of common people. Intake for wheat gluten as well as further associated proteins is recognized as activator for situation within genetically liable persons. Because of linked enteropathy, people frequently stop to thrive, anemia and chronic diarrhea owing to micronutrient (mainly folate, vitamin B12) malabsorption [38].

#### **3.2 Metformin stimulated vitamin B12 deficiency amongst patients with T2DM**

Due to lack for contradictions such as renal as well as hepatic dysfunction, current guiding principles support utilization of metformin like primary line glucose reducing mediator parallel to changes in way of life [39]. Regardless of better glycemic reducing influence, metformin is revealed for reduction of vitamin B12 status. The possibility for having metformin coupled vitamin B12 deficit can be deeply affected of growing age, metformin dosage as well as period of use. The given methods for clarification of metformin induced vitamin B12 shortage amongst people having type 2 diabetes comprise: variations of small bowel motility that induces increased growth of bacteria as well as resulting vitamin B12 deficit, viable reduction and vitamin B12 malabsorption, changes within intrinsic factor status as well as contact to tubulin endocytic receptor. Metformin hamper calcium bound assimilation for complex of vitamin B12-IF at the terminal ileum. Such inhibition consequence could be inverted using calcium medication [40].
